Comparison of 5-fluorouracil alone, 5-fluorouracil with levamisole, and 5-fluorouracil with hepatic irradiation in the treatment of patients with residual, nonmeasurable, intra-abdominal metastasis after undergoing resectionfor colorectal carcinoma

BACKGROUND. The authors conducted a randomized Phase III trial of three tre atment regimens for patients with residual, nonmeasurable, intra-abdominal metastatic disease after undergoing resection for primary colorectal carcin oma. METHODS. To be eligible for this study, patients had to be both free of oth er malignancies and capable of starting their therapy within 3-6 weeks afte r surgery. They were required to have an Eastern Cooperative Oncology Group performance status < 3; to be chemotherapy, radiation, and immunotherapy n aive; to have adequate bone marrow, renal, and hepatic function; and to pro vide written, informed consent. The patients were divided into two cohorts: patients with no demonstrable hepatic metastasis (Croup A) and patients wi th hepatic metastasis (Group B). RESULTS. The 229 patients in Group A were randomized to receive either Ei-f luorouracil (5-FU) (n = 116 patients) or 5-FU with levamisole (n = 113 pati ents). The median survival (15.4 months and 15.3 months, respectively, for Groups A and B) was virtually identical. The two groups also were similar i n terms of time to treatment progression, which was 7.9 months for group th at received 5-FU alone 7.7 months for the group that received levamisole wi th 5-FU. The 168 patients in Group B with hepatic metastasis underwent a th ree-way randomization: 5-FU alone (n = 60 patients), 5-FU with levamisole ( n = 54 patients), and 5-FU with hepatic irradiation (n = 54 patients). The median overall survival for the three treatment arms were similar, with 17. 3 months for the group that received 5-FU alone, 16 months for the group th at received 5-FU with Levamisole, and 14.4 months for the group that receiv ed hepatic irradiation in addition to 5-FU: The time to treatment failure w as 6.7 months, 6.8 months, and 8.3 months, respectively, for the three grou ps. The toxicity experienced by patients was as expected with the regimens, and no differences were observed between any of the treatment groups. The primary toxicities were hematologic and gastrointestinal. There was one tre atment-related death due to adult respiratory distress syndrome, which occu rred on the first day of the fourth cycle of 5-FU and levamisole. Other Gra de 4 toxicities included nine patients with Grade 4 leukopenia, one patient with Grade 4 sepsis, and one patient with Grade 4 gastrointestinal toxicit y, including blood loss and diarrhea. CONCLUSIONS. This study showed no treatment advantage for any of the combin ed modalities over 5-FU alone in this group of patients with intra-abdomina l, nonmeasurable disease. (C) 2001 American Cancer Society.